This proposal is designed to develop an animal model for virus- initiated, autoimmune-mediated encephalomyelitis with clinical and histological characteristics which closely parallels the symptoms of the human disease, multiple scherosis. SJL mice develop an purely autoimmune encephalomyelitis with both clinical and histological characteristics parallel to those of multiple scherosis following infection with the neurotropic JHM stain of mouse hepatitis virus. Recovery from infection is marked by intermittant clinical relapses. These relapses are characterized by inflammatory cell infiltrates in the CNS in the absence of detectable virus. Disease can be transferred from affected mice to naive recipients with spleen cells, indicative of the autoimmune nature of the disease. The ability to initiate autoimmune disease in the CNS will be exploited to enable us to distinguish between events occuring during initiation of the autoimmune encephalomyelitis and the factors responsible for relapse. Histology studies on brain and spinal cord will follow the course of the disease during the acute phase, recovery, clinical relapse and following the adoptive transfer of disease via spleen cells. The presence or absence of virus at each stage of the disease will be determined by direct recovery of virus by coculture, detection of viral antigen by immunoperoxidase staining or detection of viral genome by dot blot and in situ hybridization. Immune function studies will be initiated by determining the cell type responsible for transfer of autoimmune CNS disease by depletion experiments using cell surface specific antibodies. These studies will allow us to define the model more carefully and provide a strong basis for further investigations.